Background: Numerous studies have revealed that the abnormal expression of pyroptosis-related genes is closely related to the prognosis of lung adenocarcinoma (LUAD); however, a comprehensive analysis has yet to be conducted. This study aimed to reveal the influence of pyroptosis-related genes on the prognosis of LUAD and establish a prognostic model based on those genes, in order to evaluate the prognosis of LUAD. Methods:The data of tumor and normal samples were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Differential analysis was used to identify pyroptosis-related genes (obtained from the GeneCards database) that were differentially expressed (DE) in TCGA database. Univariate and stepwise multivariate Cox proportional hazards regression analyses were used to screen feature genes related to LUAD overall survival (OS) and construct gene signature. Gene set enrichment analysis (GSEA) was then performed to reveal potential functions related to gene signature.Finally, the Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm was used to reveal distinctions in each cell-subtype groups in the immune landscape of LUAD.Results: Overall, 26 DE genes (DEGs) associated with pyroptosis were obtained. Among them, 4 (MKI67, BTK, MST1, and TUBB6) were selected as prognostic genes and a 4-gene signature with a good prognostic performance in the TCGA and GEO was constructed. The gene signature was shown to be an independent prognostic factor of LUAD in subsequent analysis. Functional enrichment indicated that the 4-gene signature may participate in the tumorigenesis and development of LUAD through various pathways related to tumor progression to play a prognostic role in LUAD. Additionally, the results of the immune landscape indicated that the 4-gene signature may affect the prognosis of LUAD via cooperating with changes in the immune microenvironment. Conclusions:The key biomarkers and pathways identified in this study would deepen the comprehension of the molecular mechanism of pyroptosis in LUAD. More importantly, the 4-gene signature may serve as a novel potential prognostic model for LUAD.

Background/Aim: Xihuang Wan (XHW), a traditional Chinese medicine (TCM), has been used in China for a variety of cancers including lung cancer. The present study evaluated the efficacy of XHW on a Lewis lung mouse model and explored the potential mechanism via transcriptomics. Materials and Methods: The mice were randomized into 6 groups: 1) untreated control (n=10); 2) low-dose XHW; 3) medium-dose XHW; 4) high-dose XHW; 5) cisplatin; and 6) untreated blank (n=4). Lewis lung carcinoma (LLC) cells were injected subcutaneously except for the 4 mice in the blank group. The body weight and tumor length and width were measured every 3 days. RNAsequencing was performed on tumors in the high-dose XHW group and the control group. Results: XHW inhibited the growth of LLC in a syngeneic mouse model, without toxicity, with equivalent efficacy to cisplatin. RNA-sequencing demonstrated that many signaling pathways were involved in XHW-mediated inhibition of LLC, including tumor necrosis factor, estrogen, cyclic guanosine 3', 5'monophosphate-protein kinase G, apelin and the peroxisome proliferator-activated receptor signaling pathways. Conclusion: XHW inhibited LLC carcinoma through different pathways and shows clinical promise for patients who cannot tolerate platinum-based drugs.Lung cancer, with an estimated 2.2 million new cases and 1.8 million deaths in 2020, ranks second in incidence and first in mortality among all cancer types throughout the world (1). In China, lung cancer was also the second most commonly diagnosed cancer (815,563 cases) and the leading cause of cancer death (243,153 cases) in 2020 (2). First-line treatment includes surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy (3, 4). However, lung cancer still remains recalcitrant.In China, traditional Chinese medicine (TCM) has been used in clinical practice for thousands of years for a variety of diseases, including benign and malignant tumors (5-8). Xihuang Wan (XHW) was first recorded in the 18 th -century Chinese medical book Waike Zhengzhi Quansheng Ji (Lifesaving Manual of Diagnosis and Treatment of External Diseases). XHW comprises Ruxiang (Olibanum), Moyao (Myrrha), Niuhuang (Moschus), and Shexiang (Bovis Calculus). XHW has been approved by the National Medical Products Administration (NMPA) of China for the treatment of cancer (approval number Z11020073). In clinical practice, XHW has been used to treat breast (9-12), colorectal (13), liver (14, 15), cervical (16-18), and lung cancer (19)(20)(21). A systematic review and meta-analysis showed that XHW combined with chemotherapy enhanced response, prolonged overall survival, improved the quality of life of patients, and alleviated treatment-induced side effects (22).Our laboratory has previously studied Lewis-lung carcinoma (LLC) in both nude mouse and syngeneic models (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35). In the present study, we examined the anti-cancer efficacy of XHW in a syngeneic mouse model of LLC, and explored the potential mechanism of XHW by RNAsequencing...